Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 92521, USA.
Center for Glial-Neuronal Interactions, University of California, Riverside, CA 92521, USA.
Cells. 2023 Jun 23;12(13):1701. doi: 10.3390/cells12131701.
Edema formation following traumatic spinal cord injury (SCI) exacerbates secondary injury, and the severity of edema correlates with worse neurological outcome in human patients. To date, there are no effective treatments to directly resolve edema within the spinal cord. The aquaporin-4 (AQP4) water channel is found on plasma membranes of astrocytic endfeet in direct contact with blood vessels, the glia limitans in contact with the cerebrospinal fluid, and ependyma around the central canal. Local expression at these tissue-fluid interfaces allows AQP4 channels to play an important role in the bidirectional regulation of water homeostasis under normal conditions and following trauma. In this review, we consider the available evidence regarding the potential role of AQP4 in edema after SCI. Although more work remains to be carried out, the overall evidence indicates a critical role for AQP4 channels in edema formation and resolution following SCI and the therapeutic potential of AQP4 modulation in edema resolution and functional recovery. Further work to elucidate the expression and subcellular localization of AQP4 during specific phases after SCI will inform the therapeutic modulation of AQP4 for the optimization of histological and neurological outcomes.
创伤性脊髓损伤 (SCI) 后会形成水肿，加重继发性损伤，水肿的严重程度与人患者的神经功能预后相关。迄今为止，尚无有效的方法可直接解决脊髓内的水肿。水通道蛋白-4 (AQP4) 水通道位于与血管直接接触的星形胶质细胞足突的质膜上、与脑脊液接触的胶质界膜上以及中央管周围的室管膜上。这些组织-液界面上的局部表达使 AQP4 通道在正常情况下和创伤后水动态平衡的双向调节中发挥重要作用。在这篇综述中，我们考虑了有关 AQP4 在 SCI 后水肿中潜在作用的现有证据。尽管仍有更多工作要做，但总体证据表明 AQP4 通道在 SCI 后水肿的形成和消退中起着关键作用，AQP4 调节在水肿消退和功能恢复方面具有治疗潜力。进一步阐明 SCI 后特定阶段 AQP4 的表达和亚细胞定位将为 AQP4 的治疗调节提供信息，以优化组织学和神经学结果。
